Associations of systemic inflammatory indices with rheumatoid arthritis and all-cause mortality: a NHANES study with independent hospital-based replication

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease associated with substantial morbidity and increased mortality. Although several composite inflammatory indices have been proposed as accessible biomarkers, their associations with RA and long-term prognosis remain incompletely understood. We analyzed 15,545 adults from five NHANES cycles (2001–2010), including 1,075 participants with self-reported RA. Survey-weighted multivariable logistic regression was used to assess associations between inflammatory indices and prevalent RA. Among participants with RA, survey-weighted Kaplan–Meier and Cox regression analyses were used to evaluate all-cause mortality. Restricted cubic spline analyses examined potential nonlinear associations. An independent retrospective hospital-based cohort was used to assess the directional consistency of key RA-related associations. Among 15,545 participants, 1,075 had self-reported RA. In the fully adjusted models, participants in the highest RAR quartile had greater odds of prevalent self-reported RA than those in the lowest quartile (OR, 1.86; 95% CI, 1.33–2.60), whereas higher CALLY was inversely associated with RA (Q4 vs. Q1: OR, 0.58; 95% CI, 0.43–0.78); both associations remained significant after FDR correction. Among participants with self-reported RA, higher RAR was associated with a greater hazard of all-cause mortality (Q4 vs. Q1: HR, 2.48; 95% CI, 1.62–3.77), whereas higher CALLY was associated with a lower mortality hazard (Q4 vs. Q1: HR, 0.44; 95% CI, 0.31–0.61), with both associations remaining significant after FDR correction. Restricted cubic spline analyses suggested nonlinear associations for several inflammatory indices. In the independent hospital-based cohort, several key RA-related inflammatory indices showed directionally consistent associations, supporting the reproducibility of the principal RA-related findings. RAR and CALLY showed the most consistent associations with both prevalent RA and all-cause mortality. These accessible inflammatory indices may warrant further evaluation as markers of systemic inflammatory and nutritional status in RA, but prospective validation is needed before clinical application.